ESPE Abstracts (2016) 86 P-P2-870

ESPE2016 Poster Presentations Syndromes: Mechanisms and Management P2 (50 abstracts)

Children with Down’s Syndrome Show Quantitative, Phenotypical and Functional Differences of Effector T-Cells Compared to Immunocompetent Controls

Justine Schoch a , Tina Schmidt a , Anna-Maria Jung b , Michael Kästner d , Hashim Abdul-Khaliq c , Ludwig Gortner b , Martina Sester a & Tilman Rohrer b


aDepartment of Transplant and Infection Immunology, Saarland University, Homburg, Germany; bDepartment of Pediatrics and Neonatology, University Children’s Hospital of Saarland, Homburg, Germany; cDepartment of Pediatric Cardiology, University Children’s Hospital of Saarland, Homburg, Germany; dDivision of Pediatric Cardiology, University Children’s Hospital, Ulm, Germany


Background: Trisomy 21 is associated with an increased susceptibility to respiratory infections.

Objective and hypotheses: For a more detailed characterization of the adaptive immune response, we analyzed the cellular and humoral immunity to specific pathogens in blood samples of 40 children with Down’s syndrome in comparison to 51 age-matched controls.

Method: We quantitatively analyzed lymphocyte subpopulations using flow cytometry. In addition, the T-cell effector function was characterized by functional and phenotypical analysis after polyclonal stimulation with staphylococcal enterotoxin (SEB) and antigen-specific stimulation with antigens of Varicella zoster virus (VZV), Cytomegalovirus (CMV) and M.tuberculosis (tuberculin). Results were correlated with humoral immune responses.

Results: The proportion of NK-cells within the lymphocytes of children with Down’s syndrome was strikingly increased whereas the B-cell percentage was decreased. While the total amount of T-cells showed no differences, children with Down’s syndrome revealed less CD4+ and more CD4+CD8+T-cells. Within the CD4+T-cell population, we detected a higher percentage of regulatory and Th17-cells and a higher Th1/Th2 ratio as well as a higher expression of the anergy markers PD-1 and CTLA-4. Percentages of polyclonally activated cells were significantly higher in children with Down’s syndrome and showed an altered expression profile of the cytokines INFγ, TNFα and IL-2. Analysis of pathogen-specific immune responses showed an age-appropriate level of endemic infection with CMV, VZV and mycobacteria in both groups. CMV-specific cellular and humoral immunity correlated in all children. Among VZV IgG positive children, a higher percentage of VZV-specific T-cell-positive individuals were seen in the Down’s syndrome group.

Conclusion: No pronounced differences were detectable in pathogen-specific immune responses of children with Down’s syndrome and controls. Besides a general proportional shift of leukocyte and lymphocyte subpopulations, effector T-cells seem to be functionally impaired which may promote a higher susceptibility to infections. The simultaneously higher fraction of reactive effector T-cells could represent a compensatory effect of functional anergy and/or be a consequence of a more pronounced history of infection.

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